There is a significant unmet clinical need for a sensitive, accurate and convenient test to assess the excretory function of the kidneys (glomerular filtration rate, GFR). The most accurate measurement of renal function is the measured glomerular filtration rate (mGFR), which requires the use of ideal filtration markers (e.g., inulin, iothalamate, iohexol). Due to its complexity, this measurement is expensive, difficult to perform in routine clinical practice, and is typically only used in research studies or for potential kidney donors. Consequently, alternative measures of kidney function based on markers such as serum creatinine are used in complex equations to derive an estimated GFR (eGFR). The advantage of this approach is its ease of use in routine clinical practice for the assessment of kidney function. However, these methods of determining the GFR have limitations in truly assessing the kidney function; some equations under-estimate GFR and some over-estimate GFR, especially when it is in the “normal” range. Some of these limitations are likely due to the variability of serum creatinine levels which can be affected by muscle mass, diet, and some drugs, including antibiotics, which leads to variable levels among individuals and over time. The clinical consequence of this inaccuracy leads to the misdiagnosis of patients. In some cases, individuals with chronic kidney disease (CKD) are not diagnosed by current methods and thus they do not receive appropriate treatment (false negative). In other cases, individuals may be diagnosed as having CKD when in fact they do not have CKD (false positive); these individuals are then treated for a disease they do not have. More recently serum levels of cystatin C have been used to assess kidney function, but the utility of this measure of kidney function is limited by the variability of cystatin C serum levels among individuals. Thus, there is a need for a convenient and more accurate test than the currently available kidney function assessment tests to reduce the number of false negative and false positive diagnoses.
Furthermore, current assessments of kidney function (e.g., serum creatinine, cystatin C and eGFR measurements, BUN, urine albumin) are not sufficiently sensitive and/or accurate to detect early kidney disease or to monitor its progression, especially at the earliest stages of CKD when individuals are asymptomatic. Early detection of declining kidney function could prevent significant deterioration of kidney function that may occur before the problem is detected with currently available methods. A novel test with a sensitive readout that assesses and monitors an individual's kidney function would allow for earlier detection of CKD, before CKD can be detected with current methods. As a result, the overall cost of treating and managing CKD and associated complications would be reduced. With early detection of CKD, complications, including cardiovascular disease, anemia, malnutrition and bone disease, can be more effectively treated or possibly even prevented. Early detection of CKD would enable lifestyle modifications such as healthy diet, smoking cessation, weight loss, and treatment of high blood pressure, which could prevent or reduce further kidney injury, thereby reducing the need for dialysis and kidney transplant which are frequent outcomes associated with reduced kidney function and CKD.
A blood- or urine-based test to assess and/or monitor a patient's renal function by measuring the level of one or more biomarker metabolites in patients with risk factors for CKD (e.g., age over 60, hypertension, diabetes, cardiovascular disease, family history of CKD) would be clinically useful. For example, the biomarkers could comprise a test that quantitatively measures the level of a panel of biomarker metabolites whereby the increase or decrease in the level of each biomarker in the panel relative to a standard reference level are indicative of kidney function. Such biomarker test panels could replace or supplement current kidney function test results and enable physicians to better assess kidney function initially and/or to monitor kidney function in patients over time. Such a test could also be useful in assessing the effect of therapeutic interventions to slow kidney function decline.